The present invention relates to the prevention or treatment of connective tissue softening.
Injury to connective tissues such as tendons, ligaments and cartilage may occur in a number of ways. For instance, a tendon may be ruptured or torn following a sudden twist or pull on a joint to which the tendon is fixed. Connective tissue injuries may also arise due to a gross trauma such as a crush injury or an incisional wounding of a tissue. Alternatively connective tissue injuries may arise as a result of repetitive trauma to a tissue (e.g. repetitive strain injuries caused by prolonged use of pneumatic drills).
Connective tissue injuries of the limbs (e.g. tendon injuries of the fingers, wrist or legs) of humans and animals are particularly problematic.
To repair connective tissue it is necessary for the areas of tissue (e.g. the torn edges of a severed tendon) to be maintained in close proximity following which reparative processes generate a tissue which bridges the gap between undamaged tissues. The areas may be brought into close proximity by immobilising the tissues or by surgical intervention (e.g. by suturing the torn edges together).
However, during the first few days following an injury (usually up to 7 days but possibly up to 14 days) a phenomenon known as xe2x80x9csofteningxe2x80x9d occurs which can have deleterious effects on tissue repair. Softening involves the liquefaction of the extracellular matrix at the edges of damaged connective tissue.
This liquefaction represents a problem for several reasons. In the first place the softened tissue is very weak and may easily be torn leading to re-injury and even permanent disability. This is particularly problematic for load bearing connective tissues such as injured tendons in the leg. Furthermore, the weakening caused by softening can be such that the tensile strength of the connective tissue actually becomes less than it was immediately after the injury occurred. For example, 5 days after a finger tendon is sutured together the tendon often only has 10-20% of the tensile strength that it had immediately post operatively and only about 1% of the tensile strength of a uninjured tendon.
Furthermore, if surgery is used, softening is also a problem because the softened tissues may be difficult to maintain in close proximity to each other due to the fact that sutures often come out of the liquefied tissues and the torn ends may then separate preventing any repair from occurring.
In the case of repetitive strain injuries (which involve frequent xe2x80x9cre-injuryxe2x80x9d) connective tissues such as tendons and ligaments may be in a chronic xe2x80x9csoftenedxe2x80x9d state. When this is the case the tissue often has an outer sheaf of apparently normal connective tissue but comprises an inner core of liquefied tissues. Any injury to the outer sheaf may rupture the tissue with serious consequences for connective tissue function.
Connective tissue softening is highly problematic during connective tissue healing in people and animals (particularly horses and pets) and there is a need to provide medicaments that prevent connective tissue softening from occurring.
According to a first aspect of the present invention there is provided the use of a Matrix Metalloproteinase Inhibitor in the manufacture of a medicament for use in the treatment or prevention of connective tissue softening.
According to a second aspect of the present invention there is provided a method of preventing or treating connective tissue softening comprising administering to a subject in need of treatment a therapeutically effective amount of a Matrix Metalloproteinase Inhibitor.
The inventors have found that matrix metalloproteinase (MMP) inhibitors are effective for inhibiting or preventing connective tissue softening. These inhibitors may therefore be used to promote the healing of injuries to connective tissues such as tendons, ligaments and cartilage in people and animals. For example, a person with a torn tendon of the finger benefits from the administration of MMP inhibitors because the subsequent reduction in softening results in the edges of the torn tendon knitting together more quickly and with greater strength than seen for untreated tendons. MMP inhibitors are also highly suitable for administration to animals (such as dogs or horses and particularly valuable race or show animals) for the treatment or prevention of connective tissue softening and especially tendon injuries of the legs. By treating a horse with an MMP inhibitor according to the present invention it is possible to prevent, or significantly decrease the chances of, the animal becoming lame following a connective tissue injury (e.g. of a tendon). Thus the use of MMP inhibitors according to the present invention makes it less likely that such an expensive animal would need to be put down following an injury.
MMP inhibitors are particularly useful for maintaining sutures in a connective tissue (e.g. a healing tendon) and according to a third aspect of the present invention there is provided the use of a Matrix Metalloproteinase Inhibitor in the manufacture of a medicament for maintaining sutures in a connective tissue.
According to a fourth aspect of the present invention there is provided a method for maintaining sutures in a connective tissue comprising administering to a subject in need of treatment a therapeutically effective amount of a Matrix Metalloproteinase Inhibitor.
We have found that MMP inhibitors reduce tissue softening and thereby help to maintain sutures in a required position. It is preferred that MMP inhibitors are used according to the third or fourth aspects of the invention to maintain sutures in a healing tendon. This allows for improved healing of the ends of a severed tendon because the sutures are more able to maintain the severed ends of the tendon in close proximity.